Nitric oxide donor-induced p53-sensitive cell death is enhanced by Bcl-2 reduction in human neuroblastoma cells.
In human neuroblastoma SH-SY5Y cells, S-nitroso-N-acetylpenicillamine (SNAP), a nitric oxide (NO)-donor, caused cell death accompanying p53 expression, nucleosomal DNA fragmentation and cell death. In addition, SNAP-induced cell death and DNA fragmentation were enhanced by pretreatment for 4 days with N6,2'-O-dibutyryl cyclic AMP (diBu-cAMP) or staurosporine, while those were not changed by pretreatment with phorbol 12-myristate 13-acetate (PMA). Protein level of Bcl-2 was decreased by pretreatment with diBu-cAMP or staurosporine, and, on the contrary, the level was increased by pretreatment with PMA. However, these pretreatments did not change Bax protein level and SNAP-induced p53 expression. However, SNAP-treatment did not change protein levels of Bcl-2 and Bax. These results suggest that SNAP-induced p53-sensitive apoptosis is enhanced by Bcl-2 reduction, and that Bcl-2 and Bax may act downstream of p53 in SH-SY5Y cells.
Kitamura
Y
Y
Department of Neurobiology, Kyoto Pharmaceutical University, Japan.
Kamoshima
W
W
Shimohama
S
S
Nomura
Y
Y
Taniguchi
T
T
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects*; D053938:DNA Fragmentation; D019281:Dimerization; D015870:Gene Expression; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism* / Q000648:ultrastructure; D009569:Nitric Oxide / Q000378:metabolism*; D010084:Oxidation-Reduction; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000378:metabolism*; D026423:S-Nitroso-N-Acetylpenicillamine; D019311:Staurosporine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000502:physiology*; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; C494827:Bax protein, mouse; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D009569:Nitric Oxide; D003994:Bucladesine; D026423:S-Nitroso-N-Acetylpenicillamine; D010396:Penicillamine; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate